Electrode designs and methods of use for cardiovascular reflex control devices

ABSTRACT

Devices, systems and methods by which the blood pressure, nervous system activity, and neurohornonal activity may be selectively and controllably reduced by activating baroreceptors. A baroreceptor activation device is positioned near a baroreceptor, preferably in the carotid sinus. The baroreceptor activation device may utilize electrodes to activate the baroreceptors. The electrodes may be adapted for connection to the carotid arteries at or near the carotid sinus, and may be designed to minimize extraneous tissue stimulation.

[0001] This application claims priority to U.S. patent application Ser.No. 09/671,850, filed Sep. 27, 2000, entitled “Devices and Methods forCardiovascular Reflex Control”, U.S. patent application Ser. No. ______,filed on even date herewith, entitled “Stimulus Regimens forCardiovascular Reflex Control”, and U.S. patent application Ser. No.______, filed on even date herewith, entitled “Mapping Methods forCardiovascular Reflex Control Devices”, the entire disclosures of whichare hereby incorporated by reference.

FIELD OF THE INVENTION

[0002] The present invention generally relates to medical devices andmethods of use for the treatment and/or management of cardiovascular andrenal disorders. Specifically, the present invention relates to devicesand methods for controlling the baroreflex system for the treatmentand/or management of cardiovascular and renal disorders and theirunderlying causes and conditions.

BACKGROUND OF THE INVENTION

[0003] Cardiovascular disease is a major contributor to patient illnessand mortality. It also is a primary driver of health care expenditure,costing more than $326 billion each year in the United States.Hypertension, or high blood pressure, is a major cardiovascular disorderthat is estimated to affect over 50 million people in the United Satesalone. Of those with hypertension, it is reported that fewer than 30%have their blood pressure under control. Hypertension is a leading causeof heart failure and stroke. It is the primary cause of death in over42,000 patients per year and is listed as a primary or contributingcause of death in over 200,000 patients per year in the U.S.Accordingly, hypertension is a serious health problem demandingsignificant research and development for the treatment thereof.

[0004] Hypertension may occur when the body's smaller blood vessels(arterioles) constrict, causing an increase in blood pressure. Becausethe blood vessels constrict, the heart must work harder to maintainblood flow at the higher pressures. Although the body may tolerate shortperiods of increased blood pressure, sustained hypertension mayeventually result in damage to multiple body organs, including thekidneys, brain, eyes and other tissues, causing a variety of maladiesassociated therewith. The elevated blood pressure may also damage thelining of the blood vessels, accelerating the process of atherosclerosisand increasing the likelihood that a blood clot may develop. This couldlead to a heart attack and/or stroke. Sustained high blood pressure mayeventually result in an enlarged and damaged heart (hypertrophy), whichmay lead to heart failure.

[0005] Heart failure is the final common expression of a variety ofcardiovascular disorders, including ischemic heart disease. It ischaracterized by an inability of the heart to pump enough blood to meetthe body's needs and results in fatigue, reduced exercise capacity andpoor survival. It is estimated that approximately 5,000,000 people inthe United States suffer from heart failure, directly leading to 39,000deaths per year and contributing to another 225,000 deaths per year. Itis also estimated that greater than 400,000 new cases of heart failureare diagnosed each year. Heart failure accounts for over 900,000hospital admissions annually, and is the most common discharge diagnosisin patients over the age of 65 years. It has been reported that the costof treating heart failure in the United States exceeds $20 billionannually. Accordingly, heart failure is also a serious health problemdemanding significant research and development for the treatment and/ormanagement thereof.

[0006] Heart failure results in the activation of a number of bodysystems to compensate for the heart's inability to pump sufficientblood. Many of these responses are mediated by an increase in the levelof activation of the sympathetic nervous system, as well as byactivation of multiple other neurohormonal responses. Generallyspeaking, this sympathetic nervous system activation signals the heartto increase heart rate and force of contraction to increase the cardiacoutput; it signals the kidneys to expand the blood volume by retainingsodium and water; and it signals the arterioles to constrict to elevatethe blood pressure. The cardiac, renal and vascular responses increasethe workload of the heart, further accelerating myocardial damage andexacerbating the heart failure state. Accordingly, it is desirable toreduce the level of sympathetic nervous system activation in order tostop or at least minimize this vicious cycle and thereby treat or managethe heart failure.

[0007] A number of drug treatments have been proposed for the managementof hypertension, heart failure and other cardiovascular disorders. Theseinclude vasodilators to reduce the blood pressure and ease the workloadof the heart, diuretics to reduce fluid overload, inhibitors andblocking agents of the body's neurohormonal responses, and othermedicaments.

[0008] Various surgical procedures have also been proposed for thesemaladies. For example, heart transplantation has been proposed forpatients who suffer from severe, refractory heart failure.Alternatively, an implantable medical device such as a ventricularassist device (VAD) may be implanted in the chest to increase thepumping action of the heart. Alternatively, an intra-aortic balloon pump(IABP) may be used for maintaining heart function for short periods oftime, but typically no longer than one month. Other surgical proceduresare available as well.

[0009] It has been known for decades that the wall of the carotid sinus,a structure at the bifurcation of the common carotid arteries, containsstretch receptors (baroreceptors) that are sensitive to the bloodpressure. These receptors send signals via the carotid sinus nerve tothe brain, which in turn regulates the cardiovascular system to maintainnormal blood pressure (the baroreflex), in part through activation ofthe sympathetic nervous system. Electrical stimulation of the carotidsinus nerve (baropacing) has previously been proposed to reduce bloodpressure and the workload of the heart in the treatment of high bloodpressure and angina. For example, U.S. Pat. No. 6,073,048 to Kieval etal. discloses a baroreflex modulation system and method for stimulatingthe baroreflex arc based on various cardiovascular and pulmonaryparameters.

[0010] Although each of these alternative approaches is beneficial insome ways, each of the therapies has its own disadvantages. For example,drug therapy is often incompletely effective. Some patients may beunresponsive (refractory) to medical therapy. Drugs often have unwantedside effects and may need to be given in complex regimens. These andother factors contribute to poor patient compliance with medicaltherapy. Drug therapy may also be expensive, adding to the health carecosts associated with these disorders. Likewise, surgical approaches arevery costly, may be associated with significant patient morbidity andmortality and may not alter the natural history of the disease.Baropacing also has not gained acceptance. Several problems withelectrical carotid sinus nerve stimulation have been reported in themedical literature. These include the invasiveness of the surgicalprocedure to implant the nerve electrodes, and postoperative pain in thejaw, throat, face and head during stimulation. In addition, it has beennoted that high voltages sometimes required for nerve stimulation maydamage the carotid sinus nerves. Accordingly, there continues to be asubstantial and long felt need for new devices and methods for treatingand/or managing high blood pressure, heart failure and their associatedcardiovascular and nervous system disorders.

[0011] Situations may also arise in which it would be beneficial toraise the blood pressure of a patient. For example, the patient may beexperiencing a period of reduced blood pressure, or hypotension.Conditions associated with symptomatic hypotension include vasovagalreactions, orthostatic hypotension and dysautonomia. Alternatively, itmay be advantageous to augment the blood pressure of a patient in whomthe blood pressure may be normal or near normal, for example inclaudication syndromes. Therefore, a also need exists for a therapy thatcan acutely increase the blood pressure in a patient.

SUMMARY OF THE INVENTION

[0012] To address hypertension, heart failure and their associatedcardiovascular and nervous system disorders, the present inventionprovides a number of devices, systems and methods by which the bloodpressure, nervous system activity, and neurohormonal activity may beselectively and controllably regulated by activating baroreceptors. Byselectively and controllably activating baroreceptors, the presentinvention reduces excessive blood pressure, sympathetic nervous systemactivation and neurohormonal activation, thereby minimizing theirdeleterious effects on the heart, vasculature and other organs andtissues.

[0013] In an exemplary embodiment, the present invention provides asystem and method for treating a patient by inducing a baroreceptorsignal to affect a change in the baroreflex system (e.g., reduced heartrate, reduced blood pressure, etc.). The baroreceptor signal isactivated or otherwise modified by selectively activating baroreceptors.To accomplish this, the system and method of the present inventionutilize a baroreceptor activation device positioned near a baroreceptorin the carotid sinus, aortic arch, heart, common carotid arteries,subclavian arteries, and/or brachiocephalic artery. Preferably, thebaroreceptor activation device is located in the right and/or leftcarotid sinus (near the bifurcation of the common carotid artery) and/orthe aortic arch. By way of example, not limitation, the presentinvention is described with reference to the carotid sinus location.

[0014] Generally speaking, the baroreceptor activation device may beactivated, deactivated or otherwise modulated to activate one or morebaroreceptors and induce a baroreceptor signal or a change in thebaroreceptor signal to thereby affect a change in the baroreflex system.The baroreceptor activation device may be activated, deactivated, orotherwise modulated continuously, periodically, or episodically. Thebaroreceptor activation device may comprise a wide variety of deviceswhich utilize mechanical, electrical, thermal, chemical, biological, orother means to activate the baroreceptor. The baroreceptor may beactivated directly, or activated indirectly via the adjacent vasculartissue. The baroreceptor activation device may be positioned inside thevascular lumen (i.e., intravascularly), outside the vascular wall (i.e.,extravascularly) or within the vascular wall (i.e., intramurally).

[0015] For embodiments utilizing electrical means to activate thebaroreceptor, various electrode designs are provided. The electrodedesigns may be particularly suitable for connection to the carotidarteries at or near the carotid sinus, and may be designed to minimizeextraneous tissue stimulation.

[0016] A control system may be used to generate a control signal whichactivates, deactivates or otherwise modulates the baroreceptoractivation device. The control system may operate in an open-loop or aclosed-loop mode. For example, in the open-loop mode, the patient and/orphysician may directly or remotely interface with the control system toprescribe the control signal. In the closed-loop mode, the controlsignal may be responsive to feedback from a sensor, wherein the responseis dictated by a preset or programmable algorithm.

[0017] To address low blood pressure and other conditions requiringblood pressure augmentation, the present invention provides a number ofdevices, systems and methods by which the blood pressure may beselectively and controllably regulated by inhibiting or dampeningbaroreceptor signals. By selectively and controllably inhibiting ordampening baroreceptor signals, the present invention reduces conditionsassociated with low blood pressure.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018]FIG. 1 is a schematic illustration of the upper torso of a humanbody showing the major arteries and veins and associated anatomy;

[0019]FIG. 2A is a cross-sectional schematic illustration of the carotidsinus and baroreceptors within the vascular wall;

[0020]FIG. 2B is a schematic illustration of baroreceptors within thevascular wall and the baroreflex system;

[0021]FIG. 3 is a schematic illustration of a baroreceptor activationsystem in accordance with the present invention;

[0022]FIGS. 4A and 4B are schematic illustrations of a baroreceptoractivation device in the form of an internal inflatable balloon whichmechanically induces a baroreceptor signal in accordance with anembodiment of the present invention;

[0023]FIGS. 5A and 5B are schematic illustrations of a baroreceptoractivation device in the form of an external pressure cuff whichmechanically induces a baroreceptor signal in accordance with anembodiment of the present invention;

[0024]FIGS. 6A and 6B are schematic illustrations of a baroreceptoractivation device in the form of an internal deformable coil structurewhich mechanically induces a baroreceptor signal in accordance with anembodiment of the present invention;

[0025]FIGS. 6C and 6D are cross-sectional views of alternativeembodiments of the coil member illustrated in FIGS. 6A and 6B;

[0026]FIGS. 7A and 7B are schematic illustrations of a baroreceptoractivation device in the form of an external deformable coil structurewhich mechanically induces a baroreceptor signal in accordance with anembodiment of the present invention;

[0027]FIGS. 7C and 7D are cross-sectional views of alternativeembodiments of the coil member illustrated in FIGS. 7A and 7B;

[0028]FIGS. 8A and 8B are schematic illustrations of a baroreceptoractivation device in the form of an external flow regulator whichartificially creates back pressure to induce a baroreceptor signal inaccordance with an embodiment of the present invention;

[0029]FIGS. 9A and 9B are schematic illustrations of a baroreceptoractivation device in the form of an internal flow regulator whichartificially creates back pressure to induce a baroreceptor signal inaccordance with an embodiment of the present invention;

[0030]FIGS. 10A and 10B are schematic illustrations of a baroreceptoractivation device in the form of a magnetic device which mechanicallyinduces a baroreceptor signal in accordance with an embodiment of thepresent invention;

[0031]FIGS. 11A and 11B are schematic illustrations of a baroreceptoractivation device in the form of a transducer which mechanically inducesa baroreceptor signal in accordance with an embodiment of the presentinvention;

[0032]FIGS. 12A and 12B are schematic illustrations of a baroreceptoractivation device in the form of a fluid delivery device which may beused to deliver an agent which chemically or biologically induces abaroreceptor signal in accordance with an embodiment of the presentinvention;

[0033]FIGS. 13A and 13B are schematic illustrations of a baroreceptoractivation device in the form of an internal conductive structure whichelectrically or thermally induces a baroreceptor signal in accordancewith an embodiment of the present invention;

[0034]FIGS. 14A and 14B are schematic illustrations of a baroreceptoractivation device in the form of an internal conductive structure,activated by an internal inductor, which electrically or thermallyinduces a baroreceptor signal in accordance with an embodiment of thepresent invention;

[0035]FIGS. 15A and 15B are schematic illustrations of a baroreceptoractivation device in the form of an internal conductive structure,activated by an internal inductor located in an adjacent vessel, whichelectrically or thermally induces a baroreceptor signal in accordancewith an embodiment of the present invention;

[0036]FIGS. 16A and 16B are schematic illustrations of a baroreceptoractivation device in the form of an internal conductive structure,activated by an external inductor, which electrically or thermallyinduces a baroreceptor signal in accordance with an embodiment of thepresent invention;

[0037]FIGS. 17A and 17B are schematic illustrations of a baroreceptoractivation device in the form of an external conductive structure whichelectrically or thermally induces a baroreceptor signal in accordancewith an embodiment of the present invention;

[0038]FIGS. 18A and 18B are schematic illustrations of a baroreceptoractivation device in the form of an internal bipolar conductivestructure which electrically or thermally induces a baroreceptor signalin accordance with an embodiment of the present invention;

[0039]FIGS. 19A and 19B are schematic illustrations of a baroreceptoractivation device in the form of an electromagnetic field responsivedevice which electrically or thermally induces a baroreceptor signal inaccordance with an embodiment of the present invention;

[0040]FIGS. 20A and 20B are schematic illustrations of a baroreceptoractivation device in the form of an external Peltier device whichthermally induces a baroreceptor signal in accordance with an embodimentof the present invention;

[0041] FIGS. 21A-21C are schematic illustrations of a preferredembodiment of an inductively activated electrically conductivestructure;

[0042] FIGS. 22A-22F are schematic illustrations of various possiblearrangements of electrodes around the carotid sinus for extravascularelectrical activation embodiments;

[0043]FIG. 23 is a schematic illustration of a serpentine shapedelectrode for extravascular electrical activation embodiments;

[0044]FIG. 24 is a schematic illustration of a plurality of electrodesaligned orthogonal to the direction of wrapping around the carotid sinusfor extravascular electrical activation embodiments;

[0045] FIGS. 25-28 are schematic illustrations of various multi-channelelectrodes for extravascular electrical activation embodiments;

[0046]FIG. 29 is a schematic illustration of an extravascular electricalactivation device including a tether and an anchor disposed about thecarotid sinus and common carotid artery;

[0047]FIG. 30 is a schematic illustration of an alternativeextravascular electrical activation device including a plurality of ribsand a spine;

[0048]FIG. 31 is a schematic illustration of an electrode assembly forextravascular electrical activation embodiments; and

[0049]FIG. 32 is a schematic illustration of a fragment of analternative cable for use with an electrode assembly such as shown inFIG. 31.

DETAILED DESCRIPTION OF THE INVENTION

[0050] The following detailed description should be read with referenceto the drawings in which similar elements in different drawings arenumbered the same. The drawings, which are not necessarily to scale,depict illustrative embodiments and are not intended to limit the scopeof the invention.

[0051] To better understand the present invention, it may be useful toexplain some of the basic vascular anatomy associated with thecardiovascular system. Refer to FIG. 1 which is a schematic illustrationof the upper torso of a human body 10 showing some of the major arteriesand veins of the cardiovascular system. The left ventricle of the heart11 pumps oxygenated blood up into the aortic arch 12. The rightsubclavian artery 13, the right common carotid artery 14, the leftcommon carotid artery 15 and the left subclavian artery 16 branch offthe aortic arch 12 proximal of the descending thoracic aorta 17.Although relatively short, a distinct vascular segment referred to asthe brachiocephalic artery 22 connects the right subclavian artery 13and the right common carotid artery 14 to the aortic arch 12. The rightcarotid artery 14 bifurcates into the right external carotid artery 18and the right internal carotid artery 19 at the right carotid sinus 20.Although not shown for purposes of clarity only, the left carotid artery15 similarly bifurcates into the left external carotid artery and theleft internal carotid artery at the left carotid sinus.

[0052] From the aortic arch 12, oxygenated blood flows into the carotidarteries 18/19 and the subclavian arteries 13/16. From the carotidarteries 18/19, oxygenated blood circulates through the head andcerebral vasculature and oxygen depleted blood returns to the heart 11by way of the jugular veins, of which only the right internal jugularvein 21 is shown for sake of clarity. From the subclavian arteries13/16, oxygenated blood circulates through the upper peripheralvasculature and oxygen depleted blood returns to the heart by way of thesubclavian veins, of which only the right subclavian vein 23 is shown,also for sake of clarity. The heart 11 pumps the oxygen depleted bloodthrough the pulmonary system where it is re-oxygenated. There-oxygenated blood returns to the heart 11 which pumps there-oxygenated blood into the aortic arch as described above, and thecycle repeats.

[0053] Within the arterial walls of the aortic arch 12, common carotidarteries 14/15 (near the right carotid sinus 20 and left carotid sinus),subclavian arteries 13/16 and brachiocephalic artery 22 there arebaroreceptors 30. For example, as best seen in FIG. 2A, baroreceptors 30reside within the vascular walls of the carotid sinus 20. Baroreceptors30 are a type of stretch receptor used by the body to sense bloodpressure. An increase in blood pressure causes the arterial wall tostretch, and a decrease in blood pressure causes the arterial wall toreturn to its original size. Such a cycle is repeated with each beat ofthe heart. Because baroreceptors 30 are located within the arterialwall, they are able to sense deformation of the adjacent tissue, whichis indicative of a change in blood pressure. The baroreceptors 30located in the right carotid sinus 20, the left carotid sinus and theaortic arch 12 play the most significant role in sensing blood pressurethat affects the baroreflex system 50, which is described in more detailwith reference to FIG. 2B.

[0054] Refer now to FIG. 2B, which shows a schematic illustration ofbaroreceptors 30 disposed in a generic vascular wall 40 and a schematicflow chart of the baroreflex system 50. Baroreceptors 30 are profuselydistributed within the arterial walls 40 of the major arteries discussedpreviously, and generally form an arbor 32. The baroreceptor arbor 32comprises a plurality of baroreceptors 30, each of which transmitsbaroreceptor signals to the brain 52 via nerve 38. The baroreceptors 30are so profusely distributed and arborized within the vascular wall 40that discrete baroreceptor arbors 32 are not readily discernable. Tothis end, those skilled in the art will appreciate that thebaroreceptors 30 shown in FIG. 2B are primarily schematic for purposesof illustration and discussion.

[0055] Baroreceptor signals are used to activate a number of bodysystems which collectively may be referred to as the baroreflex system50. Baroreceptors 30 are connected to the brain 52 via the nervoussystem 51. Thus, the brain 52 is able to detect changes in bloodpressure, which is indicative of cardiac output. If cardiac output isinsufficient to meet demand (i.e., the heart 11 is unable to pumpsufficient blood), the baroreflex system 50 activates a number of bodysystems, including the heart 11, kidneys 53, vessels 54, and otherorgans/tissues. Such activation of the baroreflex system 50 generallycorresponds to an increase in neurohormonal activity. Specifically, thebaroreflex system 50 initiates a neurohormonal sequence that signals theheart 11 to increase heart rate and increase contraction force in orderto increase cardiac output, signals the kidneys 53 to increase bloodvolume by retaining sodium and water, and signals the vessels 54 toconstrict to elevate blood pressure. The cardiac, renal and vascularresponses increase blood pressure and cardiac output 55, and thusincrease the workload of the heart 11. In a patient with heart failure,this further accelerates myocardial damage and exacerbates the heartfailure state.

[0056] To address the problems of hypertension, heart failure, othercardiovascular disorders and renal disorders, the present inventionbasically provides a number of devices, systems and methods by which thebaroreflex system 50 is activated to reduce excessive blood pressure,autonomic nervous system activity and neurohorinonal activation. Inparticular, the present invention provides a number of devices, systemsand methods by which baroreceptors 30 may be activated, therebyindicating an increase in blood pressure and signaling the brain 52 toreduce the body's blood pressure and level of sympathetic nervous systemand neurohormonal activation, and increase parasypathetic nervous systemactivation, thus having a beneficial effect on the cardiovascular systemand other body systems.

[0057] With reference to FIG. 3, the present invention generallyprovides a system including a control system 60, a baroreceptoractivation device 70, and a sensor 80 (optional), which generallyoperate in the following manner. The sensor 80 senses and/or monitors aparameter (e.g., cardiovascular function) indicative of the need tomodify the baroreflex system and generates a signal indicative of theparameter. The control system 60 generates a control signal as afunction of the received sensor signal. The control signal activates,deactivates or otherwise modulates the baroreceptor activation device70. Typically, activation of the device 70 results in activation of thebaroreceptors 30. Alternatively, deactivation or modulation of thebaroreceptor activation device 70 may cause or modify activation of thebaroreceptors 30. The baroreceptor activation device 70 may comprise awide variety of devices which utilize mechanical, electrical, thermal,chemical, biological, or other means to activate baroreceptors 30. Thus,when the sensor 80 detects a parameter indicative of the need to modifythe baroreflex system activity (e.g., excessive blood pressure), thecontrol system 60 generates a control signal to modulate (e.g. activate)the baroreceptor activation device 70 thereby inducing a baroreceptor 30signal that is perceived by the brain 52 to be apparent excessive bloodpressure. When the sensor 80 detects a parameter indicative of normalbody function (e.g., normal blood pressure), the control system 60generates a control signal to modulate (e.g., deactivate) thebaroreceptor activation device 70.

[0058] As mentioned previously, the baroreceptor activation device 70may comprise a wide variety of devices which utilize mechanical,electrical, thermal, chemical, biological or other means to activate thebaroreceptors 30. Specific embodiments of the generic baroreceptoractivation device 70 are discussed with reference to FIGS. 4-21. In mostinstances, particularly the mechanical activation embodiments, thebaroreceptor activation device 70 indirectly activates one or morebaroreceptors 30 by stretching or otherwise deforming the vascular wall40 surrounding the baroreceptors 30. In some other instances,particularly the non-mechanical activation embodiments, the baroreceptoractivation device 70 may directly activate one or more baroreceptors 30by changing the electrical, thermal or chemical environment or potentialacross the baroreceptors 30. It is also possible that changing theelectrical, thermal or chemical potential across the tissue surroundingthe baroreceptors 30 may cause the surrounding tissue to stretch orotherwise deform, thus mechanically activating the baroreceptors 30. Inother instances, particularly the biological activation embodiments, achange in the function or sensitivity of the baroreceptors 30 may beinduced by changing the biological activity in the baroreceptors 30 andaltering their intracellular makeup and function.

[0059] All of the specific embodiments of the baroreceptor activationdevice 70 are suitable for implantation, and are preferably implantedusing a minimally invasive percutaneous translumenal approach and/or aminimally invasive surgical approach, depending on whether the device 70is disposed intravascularly, extravascularly or within the vascular wall40. The baroreceptor activation device 70 may be positioned anywherebaroreceptors 30 affecting the baroreflex system 50 are numerous, suchas in the heart 11, in the aortic arch 12, in the common carotidarteries 18/19 near the carotid sinus 20, in the subclavian arteries13/16, or in the brachiocephalic artery 22. The baroreceptor activationdevice 70 may be implanted such that the device 70 is positionedimmediately adjacent the baroreceptors 30. Alternatively, thebaroreceptor activation device 70 may be outside the body such that thedevice 70 is positioned a short distance from but proximate to thebaroreceptors 30. Preferably, the baroreceptor activation device 70 isimplanted near the right carotid sinus 20 and/or the left carotid sinus(near the bifurcation of the common carotid artery) and/or the aorticarch 12, where baroreceptors 30 have a significant impact on thebaroreflex system 50. For purposes of illustration only, the presentinvention is described with reference to baroreceptor activation device70 positioned near the carotid sinus 20.

[0060] The optional sensor 80 is operably coupled to the control system60 by electric sensor cable or lead 82. The sensor 80 may comprise anysuitable device that measures or monitors a parameter indicative of theneed to modify the activity of the baroreflex system. For example, thesensor 80 may comprise a physiologic transducer or gauge that measuresECG, blood pressure (systolic, diastolic, average or pulse pressure),blood volumetric flow rate, blood flow velocity, blood pH, O₂ or CO₂content, mixed venous oxygen saturation (SVO₂), vasoactivity, nerveactivity, tissue activity or composition. Examples of suitabletransducers or gauges for the sensor 80 include ECG electrodes, apiezoelectric pressure transducer, an ultrasonic flow velocitytransducer, an ultrasonic volumetric flow rate transducer, athermodilution flow velocity transducer, a capacitive pressuretransducer, a membrane pH electrode, an optical detector (SVO₂) or astrain gage. Although only one sensor 80 is shown, multiple sensors 80of the same or different type at the same or different locations may beutilized.

[0061] The sensor 80 is preferably positioned in a chamber of the heart11, or in/on a major artery such as the aortic arch 12, a common carotidartery 14/15, a subclavian artery 13/16 or the brachiocephalic artery22, such that the parameter of interest may be readily ascertained. Thesensor 80 may be disposed inside the body such as in or on an artery, avein or a nerve (e.g. vagus nerve), or disposed outside the body,depending on the type of transducer or gauge utilized. The sensor 80 maybe separate from the baroreceptor activation device 70 or combinedtherewith. For purposes of illustration only, the sensor 80 is shownpositioned on the right subclavian artery 13.

[0062] By way of example, the control system 60 includes a control block61 comprising a processor 63 and a memory 62. Control system 60 isconnected to the sensor 80 by way of sensor cable 82. Control system 60is also connected to the baroreceptor activation device 70 by way ofelectric control cable 72. Thus, the control system 60 receives a sensorsignal from the sensor 80 by way of sensor cable 82, and transmits acontrol signal to the baroreceptor activation device 70 by way ofcontrol cable 72.

[0063] The memory 62 may contain data related to the sensor signal, thecontrol signal, and/or values and commands provided by the input device64. The memory 62 may also include software containing one or morealgorithms defining one or more functions or relationships between thecontrol signal and the sensor signal. The algorithm may dictateactivation or deactivation control signals depending on the sensorsignal or a mathematical derivative thereof. The algorithm may dictatean activation or deactivation control signal when the sensor signalfalls below a lower predetermined threshold value, rises above an upperpredetermined threshold value or when the sensor signal indicates aspecific physiologic event.

[0064] As mentioned previously, the baroreceptor activation device 70may activate baroreceptors 30 mechanically, electrically, thermally,chemically, biologically or otherwise. In some instances, the controlsystem 60 includes a driver 66 to provide the desired power mode for thebaroreceptor activation device 70. For example if the baroreceptoractivation device 70 utilizes pneumatic or hydraulic actuation, thedriver 66 may comprise a pressure/vacuum source and the cable 72 maycomprise fluid line(s). If the baroreceptor activation device 70utilizes electrical or thermal actuation, the driver 66 may comprise apower amplifier or the like and the cable 72 may comprise electricallead(s). If the baroreceptor activation device 70 utilizes chemical orbiological actuation, the driver 66 may comprise a fluid reservoir and apressure/vacuum source, and the cable 72 may comprise fluid line(s). Inother instances, the driver 66 may not be necessary, particularly if theprocessor 63 generates a sufficiently strong electrical signal for lowlevel electrical or thermal actuation of the baroreceptor activationdevice 70.

[0065] The control system 60 may operate as a closed loop utilizingfeedback from the sensor 80, or as an open loop utilizing commandsreceived by input device 64. The open loop operation of the controlsystem 60 preferably utilizes some feedback from the transducer 80, butmay also operate without feedback. Commands received by the input device64 may directly influence the control signal or may alter the softwareand related algorithms contained in memory 62. The patient and/ortreating physician may provide commands to input device 64. Display 65may be used to view the sensor signal, control signal and/or thesoftware/data contained in memory 62.

[0066] The control signal generated by the control system 60 may becontinuous, periodic, episodic or a combination thereof, as dictated byan algorithm contained in memory 62. Continuous control signals includea constant pulse, a constant train of pulses, a triggered pulse and atriggered train of pulses. Examples of periodic control signals includeeach of the continuous control signals described above which have adesignated start time (e.g., beginning of each minute, hour or day) anda designated duration (e.g., 1 second, 1 minute, 1 hour). Examples ofepisodic control signals include each of the continuous control signalsdescribed above which are triggered by an episode (e.g., activation bythe patient/physician, an increase in blood pressure above a certainthreshold, etc.).

[0067] The control system 60 may be implanted in whole or in part. Forexample, the entire control system 60 may be carried externally by thepatient utilizing transdermal connections to the sensor lead 82 and thecontrol lead 72. Alternatively, the control block 61 and driver 66 maybe implanted with the input device 64 and display 65 carried externallyby the patient utilizing transdermal connections therebetween. As afurther alternative, the transdermal connections may be replaced bycooperating transmitters/receivers to remotely communicate betweencomponents of the control system 60 and/or the sensor 80 andbaroreceptor activation device 70.

[0068] With general reference to FIGS. 4-21, schematic illustrations ofspecific embodiments of the baroreceptor activation device 70 are shown.The design, function and use of these specific embodiments, in additionto the control system 60 and sensor 80 (not shown), are the same asdescribed with reference to FIG. 3, unless otherwise noted or apparentfrom the description. In addition, the anatomical features illustratedin FIGS. 4-20 are the same as discussed with reference to FIGS. 1, 2Aand 2B, unless otherwise noted. In each embodiment, the connectionsbetween the components 60/70/80 may be physical (e.g., wires, tubes,cables, etc.) or remote (e.g., transmitter/receiver, inductive,magnetic, etc.). For physical connections, the connection may travelintraarterially, intravenously, subcutaneously, or through other naturaltissue paths.

[0069] Refer now to FIGS. 4A and 4B which show schematic illustrationsof a baroreceptor activation device 100 in the form of an intravascularinflatable balloon. The inflatable balloon device 100 includes a helicalballoon 102 which is connected to a fluid line 104. An example of asimilar helical balloon is disclosed in U.S. Pat. No. 5,181,911 toShturman, the entire disclosure of which is hereby incorporated byreference. The balloon 102 preferably has a helical geometry or anyother geometry which allows blood perfusion therethrough. The fluid line104 is connected to the driver 66 of the control system 60. In thisembodiment, the driver 66 comprises a pressure/vacuum source (i.e., aninflation device) which selectively inflates and deflates the helicalballoon 102. Upon inflation, the helical balloon 102 expands, preferablyincreasing in outside diameter only, to mechanically activatebaroreceptors 30 by stretching or otherwise deforming them and/or thevascular wall 40. Upon deflation, the helical balloon 102 returns to itsrelaxed geometry such that the vascular wall 40 returns to its nominalstate. Thus, by selectively inflating the helical balloon 102, thebaroreceptors 30 adjacent thereto may be selectively activated.

[0070] As an alternative to pneumatic or hydraulic expansion utilizing aballoon, a mechanical expansion device (not shown) may be used to expandor dilate the vascular wall 40 and thereby mechanically activate thebaroreceptors 30. For example, the mechanical expansion device maycomprise a tubular wire braid structure that diametrically expands whenlongitudinally compressed as disclosed in U.S. Pat. No. 5,222,971 toWillard et al., the entire disclosure of which is hereby incorporated byreference. The tubular braid may be disposed intravascularly and permitsblood perfusion through the wire mesh. In this embodiment, the driver 66may comprise a linear actuator connected by actuation cables to oppositeends of the braid. When the opposite ends of the tubular braid arebrought closer together by actuation of the cables, the diameter of thebraid increases to expand the vascular wall 40 and activate thebaroreceptors 30.

[0071] Refer now to FIGS. 5A and 5B which show schematic illustrationsof a baroreceptor activation device 120 in the form of an extravascularpressure cuff. The pressure cuff device 120 includes an inflatable cuff122 which is connected to a fluid line 124. Examples of a similar cuffs122 are disclosed in U.S. Pat. No. 4,256,094 to Kapp et al. and U.S.Pat. No. 4,881,939 to Newman, the entire disclosures of which are herebyincorporated by reference. The fluid line 124 is connected to the driver66 of the control system 60. In this embodiment, the driver 66 comprisesa pressure/vacuum source (i.e., an inflation device) which selectivelyinflates and deflates the cuff 122. Upon inflation, the cuff 122expands, preferably increasing in inside diameter only, to mechanicallyactivate baroreceptors 30 by stretching or otherwise deforming themand/or the vascular wall 40. Upon deflation, the cuff 122 returns to itsrelaxed geometry such that the vascular wall 40 returns to its nominalstate. Thus, by selectively inflating the inflatable cuff 122, thebaroreceptors 30 adjacent thereto may be selectively activated.

[0072] The driver 66 may be automatically actuated by the control system60 as discussed above, or may be manually actuated. An example of anexternally manually actuated pressure/vacuum source is disclosed in U.S.Pat. No. 4,709,690 to Haber, the entire disclosure of which is herebyincorporated by reference. Examples of transdermally manually actuatedpressure/vacuum sources are disclosed in U.S. Pat. No. 4,586,501 toClaracq, U.S. Pat. No. 4,828,544 to Lane et al., and U.S. Pat. No.5,634,878 to Grundei et al., the entire disclosures of which are herebyincorporated by reference.

[0073] Those skilled in the art will recognize that other externalcompression devices may be used in place of the inflatable cuff device120. For example, a piston actuated by a solenoid may apply compressionto the vascular wall. An example of a solenoid actuated piston device isdisclosed in U.S. Pat. No. 4,014,318 to Dokum et al, and an example of ahydraulically or pneumatically actuated piston device is disclosed inU.S. Pat. No. 4,586,501 to Claracq, the entire disclosures of which arehereby incorporated by reference. Other examples include a rotary ringcompression device as disclosed in U.S. Pat. No. 4,551,862 to Haber, andan electromagnetically actuated compression ring device as disclosed inU.S. Pat. No. 5,509,888 to Miller, the entire disclosures of which arehereby incorporated by reference.

[0074] Refer now to FIGS. 6A and 6B which show schematic illustrationsof a baroreceptor activation device 140 in the form of an intravasculardeformable structure. The deformable structure device 140 includes acoil, braid or other stent-like structure 142 disposed in the vascularlumen. The deformable structure 142 includes one or more individualstructural members connected to an electrical lead 144. Each of thestructural members forming deformable structure 142 may comprise a shapememory material 146 (e.g., nickel titanium alloy) as illustrated in FIG.6C, or a bimetallic material 148 as illustrated in FIG. 6D. Theelectrical lead 144 is connected to the driver 66 of the control system60. In this embodiment, the driver 66 comprises an electric powergenerator or amplifier which selectively delivers electric current tothe structure 142 which resistively heats the structural members146/148. The structure 142 may be unipolar as shown using thesurrounding tissue as ground, or bipolar or multipolar using leadsconnected to either end of the structure 142. Electrical power may alsobe delivered to the structure 142 inductively as described hereinafterwith reference to FIGS. 14-16.

[0075] Upon application of electrical current to the shape memorymaterial 146, it is resistively heated causing a phase change and acorresponding change in shape. Upon application of electrical current tothe bimetallic material 148, it is resistively heated causing adifferential in thermal expansion and a corresponding change in shape.In either case, the material 146/148 is designed such that the change inshape causes expansion of the structure 142 to mechanically activatebaroreceptors 30 by stretching or otherwise deforming them and/or thevascular wall 40. Upon removal of the electrical current, the material146/148 cools and the structure 142 returns to its relaxed geometry suchthat the baroreceptors 30 and/or the vascular wall 40 return to theirnominal state. Thus, by selectively expanding the structure 142, thebaroreceptors 30 adjacent thereto may be selectively activated.

[0076] Refer now to FIGS. 7A and 7B which show schematic illustrationsof a baroreceptor activation device 160 in the form of an extravasculardeformable structure. The extravascular deformable structure device 160is substantially the same as the intravascular deformable structuredevice 140 described with reference to FIGS. 6A and 6B, except that theextravascular device 160 is disposed about the vascular wall, andtherefore compresses, rather than expands, the vascular wall 40. Thedeformable structure device 160 includes a coil, braid or otherstent-like structure 162 comprising one or more individual structuralmembers connected to an electrical lead 164. Each of the structuralmembers may comprise a shape memory material 166 (e.g., nickel titaniumalloy) as illustrated in FIG. 7C, or a bimetallic material 168 asillustrated in FIG. 7D. The structure 162 may be unipolar as shown usingthe surrounding tissue as ground, or bipolar or multipolar using leadsconnected to either end of the structure 162. Electrical power may alsobe delivered to the structure 162 inductively as described hereinafterwith reference to FIGS. 14-16.

[0077] Upon application of electrical current to the shape memorymaterial 166, it is resistively heated causing a phase change and acorresponding change in shape. Upon application of electrical current tothe bimetallic material 168, it is resistively heated causing adifferential in thermal expansion and a corresponding change in shape.In either case, the material 166/168 is designed such that the change inshape causes constriction of the structure 162 to mechanically activatebaroreceptors 30 by compressing or otherwise deforming the baroreceptors30 and/or the vascular wall 40. Upon removal of the electrical current,the material 166/168 cools and the structure 162 returns to its relaxedgeometry such that the baroreceptors 30 and/or the vascular wall 40return to their nominal state. Thus, by selectively compressing thestructure 162, the baroreceptors 30 adjacent thereto may be selectivelyactivated.

[0078] Refer now to FIGS. 8A and 8B which show schematic illustrationsof a baroreceptor activation device 180 in the form of an extravascularflow regulator which artificially creates back pressure adjacent thebaroreceptors 30. The flow regulator device 180 includes an externalcompression device 182, which may comprise any of the externalcompression devices described with reference to FIGS. 5A and 5B. Theexternal compression device 182 is operably connected to the driver 66of the control system 60 by way of cable 184, which may comprise a fluidline or electrical lead, depending on the type of external compressiondevice 182 utilized. The external compression device 182 is disposedabout the vascular wall distal of the baroreceptors 30. For example, theexternal compression device 182 may be located in the distal portions ofthe external or internal carotid arteries 18/19 to create back pressureadjacent to the baroreceptors 30 in the carotid sinus region 20.Alternatively, the external compression device 182 may be located in theright subclavian artery 13, the right common carotid artery 14, the leftcommon carotid artery 15, the left subclavian artery 16, or thebrachiocephalic artery 22 to create back pressure adjacent thebaroreceptors 30 in the aortic arch 12.

[0079] Upon actuation of the external compression device 182, thevascular wall is constricted thereby reducing the size of the vascularlumen therein. By reducing the size of the vascular lumen, pressureproximal of the external compression device 182 is increased therebyexpanding the vascular wall. Thus, by selectively activating theexternal compression device 182 to constrict the vascular lumen andcreate back pressure, the baroreceptors 30 may be selectively activated.

[0080] Refer now to FIGS. 9A and 9B which show schematic illustrationsof a baroreceptor activation device 200 in the form of an intravascularflow regular which artificially creates back pressure adjacent thebaroreceptors 30. The intravascular flow regulator device 200 issubstantially similar in function and use as extravascular flowregulator 180 described with reference to FIGS. 8A and 8B, except thatthe intravascular flow regulator device 200 is disposed in the vascularlumen.

[0081] Intravascular flow regulator 200 includes an internal valve 202to at least partially close the vascular lumen distal of thebaroreceptors 30. By at least partially closing the vascular lumendistal of the baroreceptors 30, back pressure is created proximal of theinternal valve 202 such that the vascular wall expands to activate thebaroreceptors 30. The internal valve 202 may be positioned at any of thelocations described with reference to the external compression device182, except that the internal valve 202 is placed within the vascularlumen. Specifically, the internal compression device 202 may be locatedin the distal portions of the external or internal carotid arteries18/19 to create back pressure adjacent to the baroreceptors 30 in thecarotid sinus region 20. Alternatively, the internal compression device202 may be located in the right subclavian artery 13, the right commoncarotid artery 14, the left common carotid artery 15, the leftsubclavian artery 16, or the brachiocephalic artery 22 to create backpressure adjacent the baroreceptors 30 in the aortic arch 12.

[0082] The internal valve 202 is operably coupled to the driver 66 ofthe control system 60 by way of electrical lead 204. The control system60 may selectively open, close or change the flow resistance of thevalve 202 as described in more detail hereinafter. The internal valve202 may include valve leaflets 206 (bi-leaflet or tri-leaflet) whichrotate inside housing 208 about an axis between an open position and aclosed position. The closed position may be completely closed orpartially closed, depending on the desired amount of back pressure to becreated. The opening and closing of the internal valve 202 may beselectively controlled by altering the resistance of leaflet 206rotation or by altering the opening force of the leaflets 206. Theresistance of rotation of the leaflets 206 may be altered utilizingelectromagnetically actuated metallic bearings carried by the housing208. The opening force of the leaflets 206 may be altered by utilizingelectromagnetic coils in each of the leaflets to selectively magnetizethe leaflets such that they either repel or attract each other, therebyfacilitating valve opening and closing, respectively.

[0083] A wide variety of intravascular flow regulators may be used inplace of internal valve 202. For example, internal inflatable balloondevices as disclosed in U.S. Pat. No. 4,682,583 to Burton et al. andU.S. Pat. No. 5,634,878 to Grundei et al., the entire disclosures ofwhich is hereby incorporated by reference, may be adapted for use inplace of valve 202. Such inflatable balloon devices may be operated in asimilar manner as the inflatable cuff 122 described with reference toFIG. 5. Specifically, in this embodiment, the driver 66 would comprisesa pressure/vacuum source (i.e., an inflation device) which selectivelyinflates and deflates the internal balloon. Upon inflation, the balloonexpands to partially occlude blood flow and create back pressure tomechanically activate baroreceptors 30 by stretching or otherwisedeforming them and/or the vascular wall 40. Upon deflation, the internalballoon returns to its normal profile such that flow is not hindered andback pressure is eliminated. Thus, by selectively inflating the internalballoon, the baroreceptors 30 proximal thereof may be selectivelyactivated by creating back pressure.

[0084] Refer now to FIGS. 10A and 10B which show schematic illustrationsof a baroreceptor activation device 220 in the form of magneticparticles 222 disposed in the vascular wall 40. The magnetic particles222 may comprise magnetically responsive materials (i.e., ferrous basedmaterials) and may be magnetically neutral or magnetically active.Preferably, the magnetic particles 222 comprise permanent magnets havingan elongate cylinder shape with north and south poles to stronglyrespond to magnetic fields. The magnetic particles 222 are actuated byan electromagnetic coil 224 which is operably coupled to the driver 66of the control system 60 by way of an electrical cable 226. Theelectromagnetic coil 224 may be implanted as shown, or located outsidethe body, in which case the driver 66 and the remainder of the controlsystem 60 would also be located outside the body. By selectivelyactivating the electromagnetic coil 224 to create a magnetic field, themagnetic particles 222 may be repelled, attracted or rotated.Alternatively, the magnetic field created by the electromagnetic coil224 may be alternated such that the magnetic particles 222 vibratewithin the vascular wall 40. When the magnetic particles are repelled,attracted, rotated, vibrated or otherwise moved by the magnetic fieldcreated by the electromagnetic coil 224, the baroreceptors 30 aremechanically activated.

[0085] The electromagnetic coil 224 is preferably placed as close aspossible to the magnetic particles 222 in the vascular wall 40, and maybe placed intravascularly, extravascularly, or in any of the alternativelocations discussed with reference to inductor shown in FIGS. 14-16. Themagnetic particles 222 may be implanted in the vascular wall 40 byinjecting a ferro-fluid or a ferro-particle suspension into the vascularwall adjacent to the baroreceptors 30. To increase biocompatibility, theparticles 222 may be coated with a ceramic, polymeric or other inertmaterial. Injection of the fluid carrying the magnetic particles 222 ispreferably performed percutaneously.

[0086] Refer now to FIGS. 11A and 11B which show schematic illustrationsof a baroreceptor activation device 240 in the form of one or moretransducers 242. Preferably, the transducers 242 comprise an arraysurrounding the vascular wall. The transducers 242 may beintravascularly or extravascularly positioned adjacent to thebaroreceptors 30. In this embodiment, the transducers 242 comprisedevices which convert electrical signals into some physical phenomena,such as mechanical vibration or acoustic waves. The electrical signalsare provided to the transducers 242 by way of electrical cables 244which are connected to the driver 66 of the control system 60. Byselectively activating the transducers 242 to create a physicalphenomena, the baroreceptors 30 may be mechanically activated.

[0087] The transducers 242 may comprise an acoustic transmitter whichtransmits sonic or ultrasonic sound waves into the vascular wall 40 toactivate the baroreceptors 30. Alternatively, the transducers 242 maycomprise a piezoelectric material which vibrates the vascular wall toactivate the baroreceptors 30. As a further alternative, the transducers242 may comprise an artificial muscle which deflects upon application ofan electrical signal. An example of an artificial muscle transducercomprises plastic impregnated with a lithium-perchlorate electrolytedisposed between sheets of polypyrrole, a conductive polymer. Suchplastic muscles may be electrically activated to cause deflection indifferent directions depending on the polarity of the applied current.

[0088] Refer now to FIGS. 12A and 12B which show schematic illustrationsof a baroreceptor activation device 260 in the form of a local fluiddelivery device 262 suitable for delivering a chemical or biologicalfluid agent to the vascular wall adjacent the baroreceptors 30. Thelocal fluid delivery device 262 may be located intravascularly,extravascularly, or intramurally. For purposes of illustration only, thelocal fluid delivery device 262 is positioned extravascularly.

[0089] The local fluid delivery device 262 may include proximal anddistal seals 266 which retain the fluid agent disposed in the lumen orcavity 268 adjacent to vascular wall. Preferably, the local fluiddelivery device 262 completely surrounds the vascular wall 40 tomaintain an effective seal. Those skilled in the art will recognize thatthe local fluid delivery device 262 may comprise a wide variety ofimplantable drug delivery devices or pumps known in the art.

[0090] The local fluid delivery device 260 is connected to a fluid line264 which is connected to the driver 66 of the control system 60. Inthis embodiment, the driver 66 comprises a pressure/vacuum source andfluid reservoir containing the desired chemical or biological fluidagent. The chemical or biological fluid agent may comprise a widevariety of stimulatory substances. Examples include veratridine,bradykinin, prostaglandins, and related substances. Such stimulatorysubstances activate the baroreceptors 30 directly or enhance theirsensitivity to other stimuli and therefore may be used in combinationwith the other baroreceptor activation devices described herein. Otherexamples include growth factors and other agents that modify thefunction of the baroreceptors 30 or the cells of the vascular tissuesurrounding the baroreceptors 30 causing the baroreceptors 30 to beactivated or causing alteration of their responsiveness or activationpattern to other stimuli. It is also contemplated that injectablestimulators that are induced remotely, as described in U.S. Pat. No.6,061,596 which is incorporated herein by reference, may be used withthe present invention.

[0091] As an alternative, the fluid delivery device 260 may be used todeliver a photochemical that is essentially inert until activated bylight to have a stimulatory effect as described above. In thisembodiment, the fluid delivery device 260 would include a light sourcesuch as a light emitting diode (LED), and the driver 66 of the controlsystem 60 would include a pulse generator for the LED combined with apressure/vacuum source and fluid reservoir described previously. Thephotochemical would be delivered with the fluid delivery device 260 asdescribed above, and the photochemical would be activated, deactivatedor modulated by activating, deactivating or modulating the LED.

[0092] As a further alternative, the fluid delivery device 260 may beused to deliver a warm or hot fluid (e.g. saline) to thermally activatethe baroreceptors 30. In this embodiment, the driver 66 of the controlsystem 60 would include a heat generator for heating the fluid, combinedwith a pressure/vacuum source and fluid reservoir described previously.The hot or warm fluid would be delivered and preferably circulated withthe fluid delivery device 260 as described above, and the temperature ofthe fluid would be controlled by the driver 66.

[0093] Refer now to FIGS. 13A and 13B which show schematic illustrationsof a baroreceptor activation device 280 in the form of an intravascularelectrically conductive structure or electrode 282. The electrodestructure 282 may comprise a self-expanding or balloon expandable coil,braid or other stent-like structure disposed in the vascular lumen. Theelectrode structure 282 may serve the dual purpose of maintaining lumenpatency while also delivering electrical stimuli. To this end, theelectrode structure 282 may be implanted utilizing conventionalintravascular stent and filter delivery techniques. Preferably, theelectrode structure 282 comprises a geometry which allows bloodperfusion therethrough. The electrode structure 282 compriseselectrically conductive material which may be selectively insulated toestablish contact with the inside surface of the vascular wall 40 atdesired locations, and limit extraneous electrical contact with bloodflowing through the vessel and other tissues.

[0094] The electrode structure 282 is connected to electric lead 284which is connected to the driver 66 of the control system 60. The driver66, in this embodiment, may comprise a power amplifier, pulse generatoror the like to selectively deliver electrical control signals tostructure 282. As mentioned previously, the electrical control signalgenerated by the driver 66 may be continuous, periodic, episodic or acombination thereof, as dictated by an algorithm contained in memory 62of the control system 60. Continuous control signals include a constantpulse, a constant train of pulses, a triggered pulse and a triggeredtrain of pulses. Periodic control signals include each of the continuouscontrol signals described above which have a designated start time and adesignated duration. Episodic control signals include each of thecontinuous control signals described above which are triggered by anepisode.

[0095] By selectively activating, deactivating or otherwise modulatingthe electrical control signal transmitted to the electrode structure282, electrical energy may be delivered to the vascular wall to activatethe baroreceptors 30. As discussed previously, activation of thebaroreceptors 30 may occur directly or indirectly. In particular, theelectrical signal delivered to the vascular wall 40 by the electrodestructure 282 may cause the vascular wall to stretch or otherwise deformthereby indirectly activating the baroreceptors 30 disposed therein.Alternatively, the electrical signals delivered to the vascular wall bythe electrode structure 282 may directly activate the baroreceptors 30by changing the electrical potential across the baroreceptors 30. Ineither case, the electrical signal is delivered to the vascular wall 40immediately adjacent to the baroreceptors 30. It is also contemplatedthat the electrode structure 282 may delivery thermal energy byutilizing a semi-conductive material having a higher resistance suchthat the electrode structure 282 resistively generates heat uponapplication of electrical energy.

[0096] Various alternative embodiments are contemplated for theelectrode structure 282, including its design, implanted location, andmethod of electrical activation. For example, the electrode structure282 may be unipolar as shown in FIGS. 13A and 13B using the surroundingtissue as ground, or bipolar using leads connected to either end of thestructure 282 as shown in FIGS. 18A and 18B. In the embodiment of FIGS.18A and 18B, the electrode structure 282 includes two or more individualelectrically conductive members 283/285 which are electrically isolatedat their respective cross-over points utilizing insulative materials.Each of the members 283/285 is connected to a separate conductorcontained within the electrical lead 284. Alternatively, an array ofbipoles may be used as described in more detail with reference to FIG.21. As a further alternative, a multipolar arrangement may be usedwherein three or more electrically conductive members are included inthe structure 282. For example, a tripolar arrangement may be providedby one electrically conductive member having a polarity disposed betweentwo electrically conductive members having the opposite polarity.

[0097] In terms of electrical activation, the electrical signals may bedirectly delivered to the electrode structure 282 as described withreference to FIGS. 13A and 13B, or indirectly delivered utilizing aninductor as illustrated in FIGS. 14-16 and 21. The embodiments of FIGS.14-16 and 21 utilize an inductor 286 which is operably connected to thedriver 66 of the control system 60 by way of electrical lead 284. Theinductor 286 comprises an electrical winding which creates a magneticfield 287 (as seen in FIG. 21) around the electrode structure 282. Themagnetic field 287 may be alternated by alternating the direction ofcurrent flow through the inductor 286. Accordingly, the inductor 286 maybe utilized to create current flow in the electrode structure 282 tothereby deliver electrical signals to the vascular wall 40 to directlyor indirectly activate the baroreceptors 30. In all embodiments, theinductor 286 may be covered with an electrically insulative material toeliminate direct electrical stimulation of tissues surrounding theinductor 286. A preferred embodiment of an inductively activatedelectrode structure 282 is described in more detail with reference toFIGS. 21A-21C.

[0098] The embodiments of FIGS. 13-16 may be modified to form acathode/anode arrangement. Specifically, the electrical inductor 286would be connected to the driver 66 as shown in FIGS. 14-16 and theelectrode structure 282 would be connected to the driver 66 as shown inFIG. 13. With this arrangement, the electrode structure 282 and theinductor 286 may be any suitable geometry and need not be coiled forpurposes of induction. The electrode structure 282 and the inductor 286would comprise a cathode/anode or anode/cathode pair. For example, whenactivated, the cathode 282 may generate a primary stream of electronswhich travel through the inter-electrode space (i.e., vascular tissueand baroreceptors 30) to the anode 286. The cathode is preferably cold,as opposed to thermionic, during electron emission. The electrons may beused to electrically or thermally activate the baroreceptors 30 asdiscussed previously.

[0099] The electrical inductor 286 is preferably disposed as close aspossible to the electrode structure 282. For example, the electricalinductor 286 may be disposed adjacent the vascular wall as illustratedin FIGS. 14A and 14B. Alternatively, the inductor 286 may be disposed inan adjacent vessel as illustrated in FIGS. 15A and 15B. If the electrodestructure 282 is disposed in the carotid sinus 20, for example, theinductor 286 may be disposed in the internal jugular vein 21 asillustrated in FIGS. 15A and 15B. In the embodiment of FIGS. 15A and15B, the electrical inductor 286 may comprise a similar structure as theelectrode structure 282. As a further alternative, the electricalinductor 286 may be disposed outside the patient's body, but as close aspossible to the electrode structure 282. If the electrode structure 282is disposed in the carotid sinus 20, for example, the electricalinductor 286 may be disposed on the right or left side of the neck ofthe patient as illustrated in FIGS. 16A and 16B. In the embodiment ofFIGS. 16A and 16B, wherein the electrical inductor 286 is disposedoutside the patient's body, the control system 60 may also be disposedoutside the patient's body.

[0100] In terms of implant location, the electrode structure 282 may beintravascularly disposed as described with reference to FIGS. 13A and13B, or extravascularly disposed as described with reference to FIGS.17A and 17B, which show schematic illustrations of a baroreceptoractivation device 300 in the form of an extravascular electricallyconductive structure or electrode 302. Except as described herein, theextravascular electrode structure 302 is the same in design, function,and use as the intravascular electrode structure 282. The electrodestructure 302 may comprise a coil, braid or other structure capable ofsurrounding the vascular wall. Alternatively, the electrode structure302 may comprise one or more electrode patches distributed around theoutside surface of the vascular wall. Because the electrode structure302 is disposed on the outside surface of the vascular wall,intravascular delivery techniques may not be practical, but minimallyinvasive surgical techniques will suffice. The extravascular electrodestructure 302 may receive electrical signals directly from the driver 66of the control system 60 by way of electrical lead 304, or indirectly byutilizing an inductor (not shown) as described with reference to FIGS.14-16.

[0101] Refer now to FIGS. 19A and 19B which show schematic illustrationsof a baroreceptor activation device 320 in the form of electricallyconductive particles 322 disposed in the vascular wall. This embodimentis substantially the same as the embodiments described with reference toFIGS. 13-18, except that the electrically conductive particles 322 aredisposed within the vascular wall, as opposed to the electricallyconductive structures 282/302 which are disposed on either side of thevascular wall. In addition, this embodiment is similar to the embodimentdescribed with reference to FIG. 10, except that the electricallyconductive particles 322 are not necessarily magnetic as with magneticparticles 222, and the electrically conductive particles 322 are drivenby an electromagnetic filed rather than by a magnetic field.

[0102] In this embodiment, the driver 66 of the control system 60comprises an electromagnetic transmitter such as an radiofrequency ormicrowave transmitter. Electromagnetic radiation is created by thetransmitter 66 which is operably coupled to an antenna 324 by way ofelectrical lead 326. Electromagnetic waves are emitted by the antenna324 and received by the electrically conductive particles 322 disposedin the vascular wall 40. Electromagnetic energy creates oscillatingcurrent flow within the electrically conductive particles 322, anddepending on the intensity of the electromagnetic radiation and theresistivity of the conductive particles 322, may cause the electricalparticles 322 to generate heat. The electrical or thermal energygenerated by the electrically conductive particles 322 may directlyactivate the baroreceptors 30, or indirectly activate the baroreceptors30 by way of the surrounding vascular wall tissue.

[0103] The electromagnetic radiation transmitter 66 and antenna 324 maybe disposed in the patient's body, with the antenna 324 disposedadjacent to the conductive particles in the vascular wall 40 asillustrated in FIGS. 19A and 19B. Alternatively, the antenna 324 may bedisposed in any of the positions described with reference to theelectrical inductor shown in FIGS. 14-16. It is also contemplated thatthe electromagnetic radiation transmitter 66 and antenna 324 may beutilized in combination with the intravascular and extravascularelectrically conductive structures 282/302 described with reference toFIGS. 13-18 to generate thermal energy on either side of the vascularwall.

[0104] As an alternative, the electromagnetic radiation transmitter 66and antenna 324 may be used without the electrically conductiveparticles 322. Specifically, the electromagnetic radiation transmitter66 and antenna 324 may be used to deliver electromagnetic radiation(e.g., RF, microwave) directly to the baroreceptors 30 or the tissueadjacent thereto to cause localized heating, thereby thermally inducinga baroreceptor 30 signal.

[0105] Refer now to FIGS. 20A and 20B which show schematic illustrationsof a baroreceptor activation device 340 in the form of a Peltier effectdevice 342. The Peltier effect device 342 may be extravascularlypositioned as illustrated, or may be intravascularly positioned similarto an intravascular stent or filter. The Peltier effect device 342 isoperably connected to the driver 66 of the control system 60 by way ofelectrical lead 344. The Peltier effect device 342 includes twodissimilar metals or semiconductors 343/345 separated by a thermaltransfer junction 347. In this particular embodiment, the driver 66comprises a power source which delivers electrical energy to thedissimilar metals or semiconductors 343/345 to create current flowacross the thermal junction 347.

[0106] When current is delivered in an appropriate direction, a coolingeffect is created at the thermal junction 347. There is also a heatingeffect created at the junction between the individual leads 344connected to the dissimilar metals or semiconductors 343/345. Thisheating effect, which is proportional to the cooling effect, may beutilized to activate the baroreceptors 30 by positioning the junctionbetween the electrical leads 344 and the dissimilar metals orsemiconductors 343/345 adjacent to the vascular wall 40.

[0107] Refer now to FIGS. 21A-21C which show schematic illustrations ofa preferred embodiment of an inductively activated electrode structure282 for use with the embodiments described with reference to FIGS.14-16. In this embodiment, current flow in the electrode structure 282is induced by a magnetic field 287 created by an inductor 286 which isoperably coupled to the driver 66 of the control system 60 by way ofelectrical cable 284. The electrode structure 282 preferably comprises amulti-filar self-expanding braid structure including a plurality ofindividual members 282 a, 282 b, 282 c and 282 d. However, the electrodestructure 282 may simply comprise a single coil for purposes of thisembodiment.

[0108] Each of the individual coil members 282 a-282 d comprising theelectrode structure 282 consists of a plurality of individual coil turns281 connected end to end as illustrated in FIGS. 21B and 21C. FIG. 21Cis a detailed view of the connection between adjacent coil turns 281 asshown in FIG. 21B. Each coil turn 281 comprises electrically isolatedwires or receivers in which a current flow is established when achanging magnetic field 287 is created by the inductor 286. The inductor286 is preferably covered with an electrically insulative material toeliminate direct electrical stimulation of tissues surrounding theinductor 286. Current flow through each coil turn 281 results in apotential drop 288 between each end of the coil turn 281. With apotential drop defined at each junction between adjacent coil turns 281,a localized current flow cell is created in the vessel wall adjacenteach junction. Thus an array or plurality of bipoles are created by theelectrode structure 282 and uniformly distributed around the vesselwall. Each coil turn 281 comprises an electrically conductive wirematerial 290 surrounded by an electrically insulative material 292. Theends of each coil turn 281 are connected by an electrically insulatedmaterial 294 such that each coil turn 281 remains electrically isolated.The insulative material 294 mechanically joins but electrically isolatesadjacent coil turns 281 such that each turn 281 responds with a similarpotential drop 288 when current flow is induced by the changing magneticfield 287 of the inductor 286. An exposed portion 296 is provided ateach end of each coil turn 281 to facilitate contact with the vascularwall tissue. Each exposed portion 296 comprises an isolated electrode incontact with the vessel wall. The changing magnetic field 287 of theinductor 286 causes a potential drop in each coil turn 281 therebycreating small current flow cells in the vessel wall corresponding toadjacent exposed regions 296. The creation of multiple small currentcells along the inner wall of the blood vessel serves to create acylindrical zone of relatively high current density such that thebaroreceptors 30 are activated. However, the cylindrical current densityfield quickly reduces to a negligible current density near the outerwall of the vascular wall, which serves to limit extraneous currentleakage to minimize or eliminate unwanted activation of extravasculartissues and structures such as nerves or muscles.

[0109] Refer now to FIGS. 22A-22F which show schematic illustrations ofvarious possible arrangements of electrodes around the carotid sinus 20for extravascular electrical activation embodiments, such asbaroreceptor activation device 300 described with reference to FIGS. 17Aand 17B. The electrode designs illustrated and described hereinafter maybe particularly suitable for connection to the carotid arteries at ornear the carotid sinus, and may be designed to minimize extraneoustissue stimulation.

[0110] In FIGS. 22A-22F, the carotid arteries are shown, including thecommon 14, the external 18 and the internal 19 carotid arteries. Thelocation of the carotid sinus 20 may be identified by a landmark bulge21, which is typically located on the internal carotid artery 19 justdistal of the bifurcation, or extends across the bifurcation from thecommon carotid artery 14 to the internal carotid artery 19.

[0111] The carotid sinus 20, and in particular the bulge 21 of thecarotid sinus, may contain a relatively high density of baroreceptors 30(not shown) in the vascular wall. For this reason, it may be desirableto position the electrodes 302 of the activation device 300 on and/oraround the sinus bulge 21 to maximize baroreceptor responsiveness and tominimize extraneous tissue stimulation.

[0112] It should be understood that the device 300 and electrodes 302are merely schematic, and only a portion of which may be shown, forpurposes of illustrating various positions of the electrodes 302 onand/or around the carotid sinus 20 and the sinus bulge 21. In each ofthe embodiments described herein, the electrodes 302 may be monopolar(electrodes are cathodes, surrounding tissue is anode or ground),bipolar (cathode-anode pairs), or tripolar (anode-cathode-anode sets).Specific extravascular electrode designs are described in more detailhereinafter.

[0113] In FIG. 22A, the electrodes 302 of the extravascular electricalactivation device 300 extend around a portion or the entirecircumference of the sinus 20 in a circular fashion. In FIG. 22B, theelectrodes 302 of the extravascular electrical activation device 300extend around a portion or the entire circumference of the sinus 20 in ahelical fashion. In the helical arrangement shown in FIG. 22B, theelectrodes 302 may wrap around the sinus 20 any number of times toestablish the desired electrode 302 contact and coverage. In thecircular arrangement shown in FIG. 22A, a single pair of electrodes 302may wrap around the sinus 20, or a plurality of electrode pairs 302 maybe wrapped around the sinus 20 as shown in FIG. 22C to establish moreelectrode 302 contact and coverage.

[0114] The plurality of electrode pairs 302 may extend from a pointproximal of the sinus 20 or bulge 21, to a point distal of the sinus 20or bulge 21 to ensure activation of baroreceptors 30 throughout thesinus 20 region. The electrodes 302 may be connected to a single channelor multiple channels as discussed in more detail hereinafter. Theplurality of electrode pairs 302 may be selectively activated forpurposes of targeting a specific area of the sinus 20 to increasebaroreceptor responsiveness, or for purposes of reducing the exposure oftissue areas to activation to maintain baroreceptor responsiveness longterm.

[0115] In FIG. 22D, the electrodes 302 extend around the entirecircumference of the sinus 20 in a criss-cross fashion. The criss-crossarrangement of the electrodes 302 establishes contact with both theinternal 19 and external 18 carotid arteries around the carotid sinus20. Similarly, in FIG. 22E, the electrodes 302 extend around all or aportion of the circumference of the sinus 20, including the internal 19and external 18 carotid arteries at the bifurcation, and in someinstances the common carotid artery 14. In FIG. 22F, the electrodes 302extend around all or a portion of the circumference of the sinus 20,including the internal 19 and external 18 carotid arteries distal of thebifurcation. In FIGS. 22E and 22F, the extravascular electricalactivation devices 300 are shown to include a substrate or basestructure 306 which may encapsulate and insulate the electrodes 302 andmay provide a means for attachment to the sinus 20 as described in moredetail hereinafter.

[0116] From the foregoing discussion with reference to FIGS. 22A-22F, itshould be apparent that there are a number of suitable arrangements forthe electrodes 302 of the activation device 300, relative to the carotidsinus 20 and associated anatomy. In each of the examples given above,the electrodes 302 are wrapped around a portion of the carotidstructure, which may require deformation of the electrodes 302 fromtheir relaxed geometry (e.g., straight). To reduce or eliminate suchdeformation, the electrodes 302 and/or the base structure 306 may have arelaxed geometry that substantially conforms to the shape of the carotidanatomy at the point of attachment. In other words, the electrodes 302and the base structure 306 may be pre-shaped to conform to the carotidanatomy in a substantially relaxed state. Alternatively, the electrodes302 may have a geometry and/or orientation that reduces the amount ofelectrode 302 strain.

[0117] For example, in FIG. 23, the electrodes 302 are shown to have aserpentine or wavy shape. The serpentine shape of the electrodes 302reduces the amount of strain seen by the electrode material when wrappedaround a carotid structure. In addition, the serpentine shape of theelectrodes increases the contact surface area of the electrode 302 withthe carotid tissue. As an alternative, the electrodes 302 may bearranged to be substantially orthogonal to the wrap direction (i.e.,substantially parallel to the axis of the carotid arteries) as shown inFIG. 24. In this alternative, the electrodes 302 each have a length anda width or diameter, wherein the length is substantially greater thanthe width or diameter. The electrodes 302 each have a longitudinal axisparallel to the length thereof, wherein the longitudinal axis isorthogonal to the wrap direction and substantially parallel to thelongitudinal axis of the carotid artery about which the device 300 iswrapped. As with the multiple electrode embodiments describedpreviously, the electrodes 302 may be connected to a single channel ormultiple channels as discussed in more detail hereinafter.

[0118] Refer now to FIGS. 25-28 which schematically illustrate variousmulti-channel electrodes for the extravascular electrical activationdevice 300. FIG. 25 illustrates a six (6) channel electrode assemblyincluding six (6) separate elongate electrodes 302 extending adjacent toand parallel with each other. The electrodes 302 are each connected tomulti-channel cable 304. Some of the electrodes 302 may be common,thereby reducing the number of channels necessary in the cable 304.

[0119] Base structure or substrate 306 may comprise a flexible andelectrically insulative material suitable for implantation, such assilicone, perhaps reinforced with a flexible material such as polyesterfabric. The base 306 may have a length suitable to wrap around all (360°) or a portion (i.e., less than 360° ) of the circumference of one ormore of the carotid arteries adjacent the carotid sinus 20. Theelectrodes 302 may extend around a portion (i.e., less than 360° such as270° , 180° or 90° ) of the circumference of one or more of the carotidarteries adjacent the carotid sinus 20. To this end, the electrodes 302may have a length that is less than (e.g., 75%, 50% or 25%) the lengthof the base 206. The electrodes 302 may be parallel, orthogonal oroblique to the length of the base 306, which is generally orthogonal tothe axis of the carotid artery to which it is disposed about.

[0120] The electrodes 302 may comprise round wire, rectangular ribbon orfoil formed of an electrically conductive and radiopaque material suchas platinum. The base structure 306 substantially encapsulates theelectrodes 302, leaving only an exposed area for electrical connectionto extravascular carotid sinus tissue. For example, each electrode 302may be partially recessed in the base 206 and may have one side exposedalong all or a portion of its length for electrical connection tocarotid tissue. Electrical paths through the carotid tissues may bedefined by one or more pairs of the elongate electrodes 302.

[0121] In all embodiments described with reference to FIGS. 25-28, themulti-channel electrodes 302 may be selectively activated for purposesof mapping and targeting a specific area of the carotid sinus 20 todetermine the best combination of electrodes 302 (e.g., individual pair,or groups of pairs) to activate for maximum baroreceptor responsiveness.Such a mapping technique is described in U.S. patent application Ser.No. ______, filed on even date herewith, entitled “Mapping Methods forCardiovascular Reflex Control Devices”, the entire disclosure of whichis hereby incorporated by reference. In addition, the multi-channelelectrodes 302 may be selectively activated for purposes of reducing theexposure of tissue areas to activation to maintain long term efficacy asdescribed in U.S. patent application Ser. No. ______, filed on even dateherewith, entitled “Stimulus Regimens for Cardiovascular ReflexControl”, the entire disclosure of which is hereby incorporated byreference. For these purposes, it may be useful to utilize more than two(2) electrode channels. Alternatively, the electrodes 302 may beconnected to a single channel whereby baroreceptors are uniformlyactivated throughout the sinus 20 region.

[0122] An alternative multi-channel electrode design is illustrated inFIG. 26. In this embodiment, the device 300 includes sixteen (16)individual electrode pads 302 connected to 16-channel cable 304 via4-channel connectors 303. In this embodiment, the circular electrodepads 302 are partially encapsulated by the base structure 306 to leaveone face of each button electrode 302 exposed for electrical connectionto carotid 5tissues. With this arrangement, electrical paths through thecarotid tissues may be d4efined by one or more pairs (bipolar) or groups(tripolar) of electrode pads 302.

[0123] A variation of the multi-channel pad-type electrode design isillustrated in FIG. 27. In this embodiment, the device 300 includessixteen (16) individual circular pad electrodes 302 surrounded bysixteen (16) rings 305, which collectively may be referred to asconcentric electrode pads 302/305. Pad electrodes 302 are connected to17-channel cable 304 via 4-channel connectors 303, and rings 305 arecommonly connected to 17-channel cable 304 via a single channelconnector 307. In this embodiment, the circular shaped electrodes 302and the rings 305 are partially encapsulated by the base structure 306to leave one face of each pad electrode 302 and one side of each ring305 exposed for electrical connection to carotid tissues. As analternative, two rings 305 may surround each electrode 302, with therings 305 being commonly connected. With these arrangements, electricalpaths through the carotid tissues may be defined between one or more padelectrode 302/ring 305 sets to create localized electrical paths.

[0124] Another variation of the multi-channel pad electrode design isillustrated in FIG. 28. In this embodiment, the device 300 includes acontrol IC chip 310 connected to 3-channel cable 304. The control chip310 is also connected to sixteen (16) individual pad electrodes 302 via4-channel connectors 303. The control chip 310 permits the number ofchannels in cable 304 to be reduced by utilizing a coding system. Thecontrol system 60 sends a coded control signal which is received by chip310. The chip 310 converts the code and enables or disables selectedelectrode 302 pairs in accordance with the code.

[0125] For example, the control signal may comprise a pulse wave form,wherein each pulse includes a different code. The code for each pulsecauses the chip 310 to enable one or more pairs of electrodes, and todisable the remaining electrodes. Thus, the pulse is only transmitted tothe enabled electrode pair(s) corresponding to the code sent with thatpulse. Each subsequent pulse would have a different code than thepreceding pulse, such that the chip 310 enables and disables a differentset of electrodes 302 corresponding to the different code. Thus,virtually any number of electrode pairs may be selectively activatedusing control chip 310, without the need for a separate channel in cable304 for each electrode 302. By reducing the number of channels in cable304, the size and cost thereof may be reduced.

[0126] Optionally, the IC chip 310 may be connected to feedback sensor80, taking advantage of the same functions as described with referenceto FIG. 3. In addition, one or more of the electrodes 302 may be used asfeedback sensors when not enabled for activation. For example, such afeedback sensor electrode may be used to measure or monitor electricalconduction in the vascular wall to provide data analogous to an ECG.Alternatively, such a feedback sensor electrode may be used to sense achange in impedance due to changes in blood volume during a pulsepressure to provide data indicative of heart rate, blood pressure, orother physiologic parameter.

[0127] Refer now to FIG. 29 which schematically illustrates anextravascular electrical activation device 300 including a supportcollar or anchor 312. In this embodiment, the activation device 300 iswrapped around the internal carotid artery 19 at the carotid sinus 20,and the support collar 312 is wrapped around the common carotid artery14. The activation device 300 is connected to the support collar 312 bycables 304, which act as a loose tether. With this arrangement, thecollar 312 isolates the activation device from movements and forcestransmitted by the cables 304 proximal of the support collar, such asmay be encountered by movement of the control system 60 and/or driver66. As an alternative to support collar 312, a strain relief (not shown)may be connected to the base structure 306 of the activation device 300at the juncture between the cables 304 and the base 306. With eitherapproach, the position of the device 300 relative to the carotid anatomymay be better maintained despite movements of other parts of the system.

[0128] In this embodiment, the base structure 306 of the activationdevice 300 may comprise molded tube, a tubular extrusion, or a sheet ofmaterial wrapped into a tube shape utilizing a suture flap 308 withsutures 309 as shown. The base structure 306 may be formed of a flexibleand biocompatible material such as silicone, which may be reinforcedwith a flexible material such as polyester fabric available under thetrade name DACRON to form a composite structure. The inside diameter ofthe base structure 306 may correspond to the outside diameter of thecarotid artery at the location of implantation, for example 6-8 mm. Thewall thickness of the base structure 306 may be very thin to maintainflexibility and a low profile, for example less than 1 mm. If the device300 is to be disposed about a sinus bulge 21, a correspondingly shapedbulge may be formed into the base structure for added support andassistance in positioning.

[0129] The electrodes 302 (shown in phantom) may comprise round wire,rectangular ribbon or foil, formed of an electrically conductive andradiopaque material such as platinum or platinum-iridium. The electrodesmay be molded into the base structure 306 or adhesively connected to theinside diameter thereof, leaving a portion of the electrode exposed forelectrical connection to carotid tissues. The electrodes 302 mayencompass less than the entire inside circumference (e.g., 300° ) of thebase structure 306 to avoid shorting. The electrodes 302 may have any ofthe shapes and arrangements described previously. For example, as shownin FIG. 29, two rectangular ribbon electrodes 302 may be used, eachhaving a width of 1 mm spaced 1.5 mm apart.

[0130] The support collar 312 may be formed similarly to base structure306. For example, the support collar may comprise molded tube, a tubularextrusion, or a sheet of material wrapped into a tube shape utilizing asuture flap 315 with sutures 313 as shown. The support collar 312 may beformed of a flexible and biocompatible material such as silicone, whichmay be reinforced to form a composite structure. The cables 304 aresecured to the support collar 312, leaving slack in the cables 304between the support collar 312 and the activation device 300.

[0131] In all extravascular embodiments described herein, includingelectrical activation embodiments, it may be desirable to secure theactivation device to the vascular wall using sutures or other fixationmeans. For example, sutures 311 may be used to maintain the position ofthe electrical activation device 300 relative to the carotid anatomy (orother vascular site containing baroreceptors). Such sutures 311 may beconnected to base structure 306, and pass through all or a portion ofthe vascular wall. For example, the sutures 311 may be threaded throughthe base structure 306, through the adventitia of the vascular wall, andtied. If the base structure 306 comprises a patch or otherwise partiallysurrounds the carotid anatomy, the comers and/or ends of the basestructure may be sutured, with additional sutures evenly distributedtherebetween. In order to minimize the propagation of a hole or a tearthrough the base structure 306, a reinforcement material such aspolyester fabric may be embedded in the silicone material. In additionto sutures, other fixation means may be employed such as staples or abiocompatible adhesive, for example.

[0132] Refer now to FIG. 30 which schematically illustrates analternative extravascular electrical activation device 300 including oneor more electrode ribs 316 interconnected by spine 317. Optionally, asupport collar 312 having one or more (non-electrode) ribs 316 may beused to isolate the activation device 300 from movements and forcestransmitted by the cables 304 proximal of the support collar 312.

[0133] The ribs 316 of the activation device 300 are sized to fit aboutthe carotid anatomy, such as the internal carotid artery 19 adjacent thecarotid sinus 20. Similarly, the ribs 316 of the support collar 312 maybe sized to fit about the carotid anatomy, such as the common carotidartery 14 proximal of the carotid sinus 20. The ribs 316 may beseparated, placed on a carotid artery, and closed thereabout to securethe device 300 to the carotid anatomy.

[0134] Each of the ribs 316 of the device 300 includes an electrode 302on the inside surface thereof for electrical connection to carotidtissues. The ribs 316 provide insulative material around the electrodes302, leaving only an inside portion exposed to the vascular wall. Theelectrodes 302 are coupled to the multi-channel cable 304 through spine317. Spine 317 also acts as a tether to ribs 316 of the support collar312, which do not include electrodes since their finction is to providesupport. The multi-channel electrode 302 functions discussed withreference to FIGS. 25-28 are equally applicable to this embodiment.

[0135] The ends of the ribs 316 may be connected (e.g., sutured) afterbeing disposed about a carotid artery, or may remain open as shown. Ifthe ends remain open, the ribs 316 may be formed of a relatively stiffmaterial to ensure a mechanical lock around the carotid artery. Forexample, the ribs 316 may be formed of polyethylene, polypropylene,PTFE, or other similar insulative and biocompatible material.Alternatively, the ribs 316 may be formed of a metal such as stainlesssteel or a nickel titanium alloy, as long as the metallic material waselectrically isolated from the electrodes 302. As a further alternative,the ribs 316 may comprise an insulative and biocompatible polymericmaterial with the structural integrity provided by metallic (e.g.,stainless steel, nickel titanium alloy, etc.) reinforcement. In thislatter alternative, the electrodes 302 may comprise the metallicreinforcement.

[0136] Refer now to FIG. 31 which schematically illustrates a specificexample of an electrode assembly for an extravascular electricalactivation device 300. In this specific example, the base structure 306comprises a silicone sheet having a length of 5.0 inches, a thickness of0.007 inches, and a width of 0.312 inches. The electrodes 302 compriseplatinum ribbon having a length of 0.47 inches, a thickness of 0.0005inches, and a width of 0.040 inches. The electrodes 302 are adhesivelyconnected to one side of the silicone sheet 306.

[0137] The electrodes 302 are connected to a modified bipolarendocardial pacing lead, available under the trade name CONIFIX fromInnomedica (now BIOMEC Cardiovascular, Inc.), model number 501112. Theproximal end of the cable 304 is connected to the control system 60 ordriver 66 as described previously. The pacing lead is modified byremoving the pacing electrode to form the cable body 304. The MP35 wiresare extracted from the distal end thereof to form two coils 318positioned side-by-side having a diameter of about 0.020 inches. Thecoils 318 are then attached to the electrodes utilizing 316 typestainless steel crimp terminals laser welded to one end of the platinumelectrodes 302. The distal end of the cable 304 and the connectionbetween the coils 318 and the ends of the electrodes 302 areencapsulated by silicone.

[0138] The cable 304 illustrated in FIG. 31 comprises a coaxial typecable including two coaxially disposed coil leads separated into twoseparate coils 318 for attachment to the electrodes 302. An alternativecable 304 construction is illustrated in FIG. 32. FIG. 32 illustrates analternative cable body 304 which may be formed in a curvilinear shapesuch as a sinusoidal configuration, prior to implantation. Thecurvilinear configuration readily accommodates a change in distancebetween the device 300 and the control system 60 or the driver 66. Sucha change in distance may be encountered during flexion and/or extensionof the neck of the patient after implantation.

[0139] In this alternative embodiment, the cable body 304 may comprisetwo or more conductive wires 304 a arranged coaxially or collinearly asshown. Each conductive wire 304 a may comprise a multifilament structureof suitable conductive material such as stainless steel or MP35N. Aninsulative material may surround the wire conductors 304 a individuallyand/or collectively. For purposes of illustration only, a pair ofelectrically conductive wires 304 a having an insulative materialsurrounding each wire 304 a individually is shown. The insulated wires304 a may be connected by a spacer 304 b comprising, for example, aninsulative material. An additional jacket of suitable insulativematerial may surround each of the conductors 304 a. The insulativejacket may be formed to have the same curvilinear shape of the insulatedwires 304 a to help maintain the shape of the cable body 304 duringimplantation.

[0140] If a sinusoidal configuration is chosen for the curvilinearshape, the amplitude (A) may range from 1 mm to 10 mm, and preferablyranges from 2 mm to 3 mm. The wavelength (WL) of the sinusoid may rangefrom 2 mm to 20 mm, and preferably ranges from 4 mm to 10 mm. Thecurvilinear or sinusoidal shape may be formed by a heat settingprocedure utilizing a fixture which holds the cable 304 in the desiredshape while the cable is exposed to heat. Sufficient heat is used toheat set the conductive wires 304 a and/or the surrounding insulativematerial. After cooling, the cable 304 may be removed from the fixture,and the cable 304 retains the desired shape.

[0141] To address low blood pressure and other conditions requiringblood pressure augmentation, some of the baroreceptor activation devicesdescribed previously may be used to selectively and controllablyregulate blood pressure by inhibiting or dampening baroreceptor signals.By selectively and controllably inhibiting or dampening baroreceptorsignals, the present invention reduces conditions associated with lowblood pressure as described previously. Specifically, the presentinvention would function to increase the blood pressure and level ofsympathetic nervous system activation by inhibiting or dampening theactivation of baroreceptors.

[0142] This may be accomplished by utilizing mechanical, thermal,electrical and chemical or biological means. Mechanical means may betriggered off the pressure pulse of the heart to mechanically limitdeformation of the arterial wall. For example, either of the externalcompression devices 120/160 described previously may be used to limitdeformation of the arterial wall. Alternatively, the externalcompression device may simply limit diametrical expansion of thevascular wall adjacent the baroreceptors without the need for a triggeror control signal.

[0143] Thermal means may be used to cool the baroreceptors 30 andadjacent tissue to reduce the responsiveness of the baroreceptors 30 andthereby dampen baroreceptor signals. Specifically, the baroreceptor 30signals may be dampened by either directly cooling the baroreceptors 30,to reduce their sensitivity, metabolic activity and function, or bycooling the surrounding vascular wall tissue thereby causing the wall tobecome less responsive to increases in blood pressure. An example ofthis approach is to use the cooling effect of the Peltier device 340.Specifically, the thermal transfer junction 347 may be positionedadjacent the vascular wall to provide a cooling effect. The coolingeffect may be used to dampen signals generated by the baroreceptors 30.Another example of this approach is to use the fluid delivery device 260to deliver a cool or cold fluid (e.g. saline). In this embodiment, thedriver 66 would include a heat exchanger to cool the fluid and thecontrol system 60 may be used to regulate the temperature of the fluid,thereby regulating the degree of baroreceptor 30 signal dampening.

[0144] Electrical means may be used to inhibit baroreceptor 30activation by, for example, hyperpolarizing cells in or adjacent to thebaroreceptors 30. Examples of devices and method of hyperpolarizingcells are disclosed in U.S. Pat. No. 5,814,079 to Kieval, and U.S. Pat.No. 5,800,464 to Kieval, the entire disclosures of which are herebyincorporated by reference. Such electrical means may be implementedusing any of the embodiments discussed with reference to FIGS. 13-18 and21.

[0145] Chemical or biological means may be used to reduce thesensitivity of the baroreceptors 30. For example, a substance thatreduces baroreceptor sensitivity may be delivered using the fluiddelivery device 260 described previously. The desensitizing agent maycomprise, for example, tetrodotoxin or other inhibitor of excitabletissues. From the foregoing, it should be apparent to those skilled inthe art that the present invention provides a number of devices, systemsand methods by which the blood pressure, nervous system activity, andneurohormonal activity may be selectively and controllably regulated byactivating baroreceptors or by inhibiting/dampening baroreceptorsignals. Thus, the present invention may be used to increase or decreaseblood pressure, sympathetic nervous system activity and neurohormonalactivity, as needed to minimize deleterious effects on the heart,vasculature and other organs and tissues.

[0146] The baroreceptor activation devices described previously may alsobe used to provide antiarrhythmic effects. It is well known that thesusceptibility of the myocardium to the development of conductiondisturbances and malignant cardiac arrhythmias is influenced by thebalance between sympathetic and parasympathetic nervous systemstimulation to the heart. That is, heightened sympathetic nervous systemactivation, coupled with decreased parasympathetic stimulation,increases the irritability of the myocardium and likelihood of anarrhythmia. Thus, by decreasing the level of sympathetic nervous systemactivation and enhancing the level of parasympathetic activation, thedevices, systems and methods of the current invention may be used toprovide a protective effect against the development of cardiacconduction disturbances.

[0147] Those skilled in the art will recognize that the presentinvention may be manifested in a variety of forms other than thespecific embodiments described and contemplated herein. Accordingly,departures in form and detail may be made without departing from thescope and spirit of the present invention as described in the appendedclaims.

What is claimed is:
 1. A method of disposing a baroreceptor activationdevice on a carotid sinus of a patient, the carotid sinus having acircumference, the method comprising the steps of: providing abaroreceptor activation device having a base and a plurality ofelectrodes; and positioning the device proximate the carotid sinus suchthat the base extends around at least a substantial portion of thecircumference of the carotid sinus and the electrodes extend around thecarotid sinus less than the base.
 2. A method as in claim 1, wherein thestep of positioning the device comprises wrapping the base around thecarotid sinus.
 3. A method as in claim 2, wherein the base is wrapped ina circular manner.
 4. A method as in claim 2, wherein the base iswrapped in a helical manner.
 5. A method as in claim 1, wherein thepatient has an internal carotid artery, and wherein the step ofpositioning the device proximate the carotid sinus comprises wrappingthe base around the internal carotid artery adjacent the carotid sinus.6. A method as in claim 1, wherein the patient has an internal carotidartery and an external carotid artery, and wherein the step ofpositioning the device proximate the carotid sinus comprises wrappingthe base around the internal and external carotid arteries adjacent thecarotid sinus.
 7. A method as in claim 1, wherein the patient has acommon carotid artery, and wherein the step of positioning the deviceproximate the carotid sinus comprises wrapping the base around thecommon carotid artery adjacent the carotid sinus.
 8. A method as inclaim 1, wherein more than two electrodes are positioned proximate thecarotid sinus.
 9. A method as in claim 8, wherein the electrodes arespaced about at least a portion of the circumference of the carotidsinus.
 10. A method as in claim 9, wherein the electrodes compriseelectrode pads which are distributed about at least a portion of thecircumference of the carotid sinus in a grid pattern.
 11. A method as inclaim 9, wherein the electrodes comprise elongate electrodes whichextend adjacent to and parallel with each other about at least a portionof the circumference of the carotid sinus.
 12. A method as in claim 11,wherein the carotid sinus has a longitudinal axis, and wherein theelectrodes are positioned substantially parallel to the longitudinalaxis.
 13. A method as in claim 11, wherein the carotid sinus has alongitudinal axis, and wherein the electrodes are positionedsubstantially orthogonal to the longitudinal axis.
 14. A method as inclaim 11, wherein the carotid sinus has a longitudinal axis, and whereinthe electrodes are positioned substantially oblique to the longitudinalaxis.
 15. A method as in claim 1, wherein the electrodes extend aroundless than 270° of the circumference of the carotid sinus.
 16. A methodas in claim 1, wherein the electrodes extend around less than 180° ofthe circumference of the carotid sinus.
 17. A method as in claim 1,wherein the electrodes extend around less than 90° of the circumferenceof the carotid sinus.
 18. A method as in claim 1, wherein the base hasfirst and second ends, and wherein the base extends around the carotidsinus and the ends are joined.
 19. A method as in claim 1, wherein thebase has first and second ends, and wherein the ends of the base extendaround at least half of the circumference of the carotid sinus and thebase has sufficient structural integrity to grasp the carotid sinus. 20.A method of disposing a baroreceptor activation device on a carotidsinus of a patient, the carotid sinus having a circumference, the methodcomprising the steps of: providing a baroreceptor activation devicehaving a base and a plurality of electrodes; and positioning the deviceproximate the carotid sinus such that the electrodes are spaced about atleast a portion of the circumference of the carotid sinus.
 21. A methodas in claim 20, wherein more than two electrodes are spaced about atleast a portion of the circumference of the carotid sinus.
 22. A methodas in claim 20, wherein the electrodes comprise electrode pads which aredistributed about at least a portion of the circumference of the carotidsinus in a grid pattern.
 23. A method as in claim 20, wherein theelectrodes comprise elongate electrodes which extend adjacent to andparallel with each other about at least a portion of the circumferenceof the carotid sinus.
 24. A method as in claim 23, wherein the carotidsinus has a longitudinal axis, and wherein the electrodes are positionedsubstantially parallel to the longitudinal axis.
 25. A method as inclaim 23, wherein the carotid sinus has a longitudinal axis, and whereinthe electrodes are positioned substantially orthogonal to thelongitudinal axis.
 26. A method as in claim 23, wherein the carotidsinus has a longitudinal axis, and wherein the electrodes are positionedsubstantially oblique to the longitudinal axis.
 27. A method as in claim20, wherein the electrodes extend around less than 360° of thecircumference of the carotid sinus.
 28. A method as in claim 20, whereinthe electrodes extend around less than 270° of the circumference of thecarotid sinus.
 29. A method as in claim 20, wherein the electrodesextend around less than 180° of the circumference of the carotid sinus.30. A method as in claim 20, wherein the electrodes extend around lessthan 90° of the circumference of the carotid sinus.
 31. A baroreceptoractivation device for activating a baroreceptor in a carotid sinus of apatient, the carotid sinus having a circumference, the devicecomprising: a base having a length sufficient to extend around at leasta substantial portion of the circumference of the carotid sinus; and oneor more electrodes connected to the base, the electrodes having a lengthless than the length of the base.
 32. A baroreceptor activation deviceas in claim 31, comprising more than two electrodes positioned adjacenteach other on the base.
 33. A baroreceptor activation device as in claim32, wherein the electrodes comprise electrode pads which are distributedabout at least a portion of the base in a grid pattern.
 34. Abaroreceptor activation device as in claim 33, wherein each pad definestwo concentric electrodes.
 35. A baroreceptor activation device as inclaim 32, wherein the electrodes comprise elongate electrodes whichextend adjacent to and parallel with each other on the base.
 36. Abaroreceptor activation device as in claim 35, wherein the electrodesare positioned substantially parallel to the length of the base.
 37. Abaroreceptor activation device as in claim 35, wherein the electrodesare positioned substantially orthogonal to the length of the base.
 38. Abaroreceptor activation device as in claim 32, wherein the electrodescomprise non-linear elongate electrodes which extend adjacent to eachother on the base.
 39. A baroreceptor activation device as in claim 31,wherein the electrodes extend less than 75% of the length of the base.40. A baroreceptor activation device as in claim 31, wherein theelectrodes extend less than 50% of the length of the base.
 41. Abaroreceptor activation device as in claim 31, wherein the electrodesextend less than 25% of the length of the base.
 42. A baroreceptoractivation device as in claim 31, wherein the base has first and secondends, and wherein the ends are adapted to be joined.
 43. A baroreceptoractivation device as in claim 31, wherein the base has sufficientstructural integrity to grasp the carotid sinus.
 44. A baroreceptoractivation device for activating a baroreceptor in a carotid sinus of apatient, the device comprising at least one electrode having anon-linear shape along its length, the electrode assembly adapted to beplaced on the carotid sinus such that the non-linear shaped length runsgenerally orthogonal to a longitudinal axis of the carotid sinus.
 45. Abaroreceptor activation device for activating a baroreceptor in acarotid sinus of a patient, the device comprising a plurality ofelectrodes each with a length and a width, the length beingsubstantially greater then the width, the electrodes being adjacent andgenerally parallel to one another, the electrode assembly adapted to beplaced on the carotid sinus such that the length of the electrodes runsgenerally parallel to a longitudinal axis of the carotid sinus.
 46. Abaroreceptor activation device for activating a baroreceptor in acarotid sinus of a patient, the device comprising a plurality ofconcentric electrodes, the electrode assembly adapted to be placed onthe carotid sinus.
 47. A method of disposing a baroreceptor activationdevice on a carotid sinus of a patient, the carotid sinus vascular wall,the method comprising the steps of: providing a baroreceptor activationdevice having a base and a plurality of electrodes; positioning thedevice proximate the carotid sinus; and suturing the base to thevascular wall.